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J Mol Cell Biol. 2014 Aug;6(4):312-23. doi: 10.1093/jmcb/mju026. Epub 2014 May 28.

The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells.

Author information

1
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
2
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany Present address: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, 140306 Punjab, India.
3
NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
4
NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany Present address: Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
5
NMR Spectroscopy, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany Present address: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Cracow, Poland.
6
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany jentsch@biochem.mpg.de.

Abstract

Different from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast; however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing.

KEYWORDS:

Hub1; apoptosis; spliceosome; splicing; ubiquitin-like proteins

PMID:
24872507
PMCID:
PMC4141198
DOI:
10.1093/jmcb/mju026
[Indexed for MEDLINE]
Free PMC Article

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